Search Results (17)

Primary bone tumors encompass a heterogeneous spectrum ranging from benign entities to highly aggressive sarcomas. This review aims to summarize the current role and future perspectives of nuclear medicine in the diagnosis, staging, and management of primary bone tumors. Accurate diagnosis and staging are critical yet challenging due to histologic heterogeneity and overlapping imaging features. While radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) remain essential, nuclear medicine provides a complementary functional perspective by assessing bone turnover, vascularity, and glucose metabolism. Bone scintigraphy is highly sensitive for skeletal lesions and useful for detecting skip lesions or multifocal disease, although its specificity is limited. Hybrid single-photon emission computed tomography (SPECT)/CT enhances diagnostic confidence through precise anatomic localization and quantitation. [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET)/CT, by directly visualizing tumor metabolism, has become a cornerstone in osteosarcoma and Ewing sarcoma management, demonstrating superiority over bone scintigraphy for detecting skeletal metastases. In chondrosarcoma, [¹⁸F]FDG uptake correlates with histologic grade, although overlap with benign cartilage tumors complicates interpretation. Future directions include the integration of quantitative SPECT, artificial intelligence, and novel tracers such as [¹⁸F]sodium fluoride and [⁶⁸Ga]Ga-fibroblast activation protein inhibitor (FAPI). Collectively, nuclear medicine imaging is becoming a key element in musculoskeletal oncology, offering unique biological insights that complement anatomic imaging and contribute to improved patient management. Full article

Background: Lafora disease (LD) is an ultra-rare and fatal neurodegenerative disorder with limited therapeutic options. Current treatments primarily address symptoms, with modest efficacy in halting disease progression, thus highlighting the urgent need for novel therapeutic approaches. Gene therapy, antisense oligonucleotides, and recombinant enzymes have recently been, and still are, under investigation. Drug repurposing may offer a promising approach to identify new, possibly effective, therapies. Methods: This study aims to investigate the conditions for repurposing empagliflozin, an SGLT2 (sodium/glucose cotransporter-2) inhibitor, as a potential treatment for LD and to establish a clinical protocol. Clinical phase: This 12-month prospective observational study will assess the safety and clinical efficacy of empagliflozin in two patients with early to intermediate LD stage. The primary endpoints will include changes in the severity of epilepsy and cognitive function, while the secondary endpoints will assess motor function, global function, and autonomy. Multiple clinical and instrumental evaluations (including MRI and PET with ¹⁸F-fluorodeoxyglucose) will be performed before and during treatment. Safety monitoring will include regular clinical assessments and reports of adverse events. Preclinical phase: In silico studies (using both molecular docking calculations and reverse ligand-based screening) and in vitro cell-based assays will allow us to investigate the effects of empagliflozin (and other gliflozins) on some key targets likely implicated in LD pathogenesis, such as GLUT1, GLUT3, glycogen synthase (hGYS), and glycogen phosphorylase (GP), as suggested in the literature and digital platforms for in silico target fishing. Results: The expected outcome of this study is twofold, i.e., (i) assessing the safety and tolerability of empagliflozin in LD patients and (ii) gathering preliminary data on its potential efficacy in improving clinical and neurologic features. Additionally, the in silico and in vitro studies may provide new insights into the mechanisms through which empagliflozin may exert its therapeutic effects in LD. Conclusion: The findings of this study are expected to provide evidence in support of the repurposing of empagliflozin for the treatment of LD. Full article

Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the pathological processes of PTSD. The N6-methyladenosine (m⁶A) methylation of RNAs in the hippocampus is known to play a significant role in regulating the brain’s response to stress and emotional disorders. Methods: This study aimed to comprehensively analyze the roles of transcriptome-wide m⁶A modifications of the hippocampus in the BLA DBS treatment of a PTSD mouse model using m⁶A sequencing. Results: Significant alterations in functional connectivity between the ventral hippocampus (vHPC) and BLA were observed in foot shock (FS) mice through functional magnetic resonance imaging (fMRI) analysis. Furthermore, we observed that the expression of the key m⁶A methyltransferase enzyme, METTL3, in the FS and BLA DBS groups was higher than that in the control group. At the same time, both FS and BLA DBS induced the widespread m⁶A methylation of RNAs in the vHPC. Gene ontology (GO) enrichment analysis revealed that FS altered methylation in metabolic, developmental, and cytoskeletal pathways, while BLA DBS targeted metabolic, cell cycle, and neuroplasticity-related genes. Additionally, BLA DBS reversed the aberrant methylation of genes associated with multiple functional pathways induced by FS, including those related to cholinergic transmission, sodium and calcium ion homeostasis, and stress hormone responsiveness. We identified a set of RNAs with methylation changes that were reversed by BLA DBS in the FS vs. Ctrl (control) comparison, including those associated with cholinergic transmission, sodium and calcium ion balance, and stress hormone response. Additionally, we detected several specific BLA DBS-related genes through MeRIP-qPCR, indicating that DBS influences crucial genes linked to calcium signaling and synaptic plasticity. Conclusions: We draw two conclusions from these findings: BLA DBS may alleviate PTSD-like symptoms by reversing FS-induced methylation changes and by altering the methylation levels of crucial genes. These findings indicate that epigenetic m⁶A modifications in the vHPC may play an important role in the amelioration of PTSD using BLA DBS. Full article

Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden cardiac deaths. Early detection of vulnerable plaque is crucial for clinicians to implement appropriate risk-mitigation treatment strategies, offer timely interventions, and prevent potentially life-threatening events. There is an imperative clinical need to develop practical diagnostic pathways that utilize non-invasive means to risk-stratify symptomatic patients. Since the early 1990s, the identification of vulnerable plaque in clinical practice has primarily relied on invasive imaging techniques. In the last two decades, CT coronary angiogram (CTCA) has rapidly evolved into the prevalent non-invasive diagnostic modality for assessing coronary anatomy. There are now validated plaque appearances on CTCA correlating with plaque vulnerability. It is worth noting that in clinical practice, most CTCA reports omit mention of vulnerable plaque details because spatial resolution (0.3–0.5 mm) is often insufficient to reliably detect some crucial features of vulnerable plaques, such as thin fibrous caps. Additionally, accurately identifying vulnerable plaque features requires substantial expertise and time, which many cardiologists or radiologists may lack in routine reporting. Cardiac magnetic resonance imaging (cMRI) is also non-invasive and allows simultaneous anatomic and functional assessment of coronary plaques. Despite several decades of research and development, routine clinical application of cMRI in coronary plaque imaging remains hampered by complex imaging protocols, inconsistent image quality, and cost. Molecular imaging with radiotracers, specifically positron emission tomography (PET) with sodium fluoride (Na¹⁸F PET), have demonstrated significant potential as a sensitive and specific imaging procedure for diagnosing vulnerable coronary artery plaque. The study protocol is robust and brief, requiring minimal patient preparation. Compared to CTCA and cMRI, the diagnostic accuracy of this test is less dependent on the experience and expertise of the readers. Furthermore, validated automated quantitative algorithms complement the visual interpretation of the study, enhancing confidence in the diagnosis. This combination of factors makes Na¹⁸F PET a promising tool in cardiology for identifying high-risk coronary plaques. Full article

Background: Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, well-encapsulated, and slow-growing tumor that originates from Schwann cells, which form the myelin sheath around the vestibulocochlear nerve (VIII cranial nerve). The surgical treatment of this condition presents a challenging task for surgeons, as the tumor’s location and size make it difficult to remove without causing damage to the surrounding structures. In recent years, fluorescein sodium (FS) has been proposed as a tool to enhance surgical outcomes in VS surgery. This essay will provide an analytical comparison of the use of FS in VS surgery, evaluating its benefits and limitations and comparing surgical outcomes with and without FS-assisted surgery. Methods: In a retrospective study conducted at San Filippo Neri Hospital, we examined VS cases that were operated on between January 2017 and December 2023. The patients were divided into two groups: group A, which consisted of patients who underwent surgery without the use of FS until January 2020 (102 cases), and group B, which included patients who underwent surgery with FS after January 2020 (55 cases). All operations were performed using the retrosigmoid approach, and tumor size was classified according to the Koos, et al. classification system. The extent of surgical removal was evaluated using both the intraoperative surgeon’s opinion and postoperative MRI imaging. Preoperatively and postoperatively, facial nerve function and hearing were assessed. In group B, FS was used to assist the surgical procedures, which were performed using a surgical microscope equipped with an integrated fluorescein filter. Postoperative clinical and MRI controls were performed at six months and annually, with no patients lost to follow-up. Results: This study investigated the impact of intraoperative fluorescein exposure on tumor resection and clinical outcomes in patients with VS. The study found a statistically significant difference in the tumor resection rates between patients who received fluorescein intraoperatively (p = 0.037). Further analyses using the Koos classification system revealed a significant effect of fluorescein exposure, particularly in the Koos 3 subgroup (p = 0.001). Notably, no significant differences were observed in hearing loss or facial nerve function between the two groups. A Spearman correlation analysis revealed a positive correlation between tumor size and Koos, age, and size, but no significant correlation was found between facial nerve function tests. Conclusions: FS-assisted surgery for VS may potentially enhance tumor resection, allowing for more comprehensive tumor removal. Full article

Introduction: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. Materials and methods: A systematic review was conducted in MEDLINE’s electronic database from inception to December 2023 using various combinations of keywords such as “luto” [All Fields] OR “lower urinary tract obstruction” [All Fields] OR “urethral valves” [All Fields] OR “megacystis” [All Fields] OR “urethral atresia” [All Fields] OR “megalourethra” [All Fields] AND “prenatal ultrasound” [All Fields] OR “maternal ultrasound” [All Fields] OR “ob-stetric ultrasound” [All Fields] OR “anhydramnios” [All Fields] OR “oligohydramnios” [All Fields] OR “renal echogenicity” [All Fields] OR “biomarkers” [All Fields] OR “fetal urine” [All Fields] OR “amniotic fluid” [All Fields] OR “beta2 microglobulin” [All Fields] OR “osmolarity” [All Fields] OR “proteome” [All Fields] AND “outcomes” [All Fields] OR “prognosis” [All Fields] OR “staging” [All Fields] OR “prognostic factors” [All Fields] OR “predictors” [All Fields] OR “renal function” [All Fields] OR “kidney function” [All Fields] OR “renal failure” [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. Results: Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and β2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; β2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of β2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, p-value < 0.05). Conclusions: Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention. Full article

Thanks to technical advances in the field of medical imaging, it is now possible to study key features of renal anatomy and physiology, but so far poorly explored due to the inherent difficulties in studying both the metabolism and vasculature of the human kidney. In this narrative review, we provide an overview of recent research findings on renal perfusion, oxygenation, and substrate uptake. Most studies evaluating renal perfusion with positron emission tomography (PET) have been performed in healthy controls, and specific target populations like obese individuals or patients with renovascular disease and chronic kidney disease (CKD) have rarely been assessed. Functional magnetic resonance (fMRI) has also been used to study renal perfusion in CKD patients, and recent studies have addressed the kidney hemodynamic effects of therapeutic agents such as glucagon-like receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) in an attempt to characterise the mechanisms leading to their nephroprotective effects. The few available studies on renal substrate uptake are discussed. In the near future, these imaging modalities will hopefully become widely available with researchers more acquainted with them, gaining insights into the complex renal pathophysiology in acute and chronic diseases. Full article

Sodium imbalance is a hallmark of chronic kidney disease (CKD). Excess tissue sodium in CKD is associated with hypertension, inflammation, and cardiorenal disease. Sodium magnetic resonance imaging (²³Na MRI) has been increasingly utilized in CKD clinical trials especially in the past few years. These studies have demonstrated the association of excess sodium tissue accumulation with declining renal function across whole CKD spectrum (early- to end-stage), biomarkers of systemic inflammation, and cardiovascular dysfunction. In this article, we review recent advances of ²³Na MRI in CKD and discuss its future role with a focus on the skin, the heart, and the kidney itself. Full article

The aim of this review is to identify possible structural abnormalities of BrS and their potential association with symptoms, risk stratification, and prognosis. (1) Background: BrS has always been considered a purely electrical disease and imaging techniques do not currently play a specific role in the diagnosis of this arrhythmic syndrome. Some authors have recently hypothesized the presence of structural and functional abnormalities. Therefore, several studies investigated the presence of pathological features in echocardiography and cardiac magnetic resonance imaging (MRI) in patients with BrS, but results were controversial. (2) Methods: We performed a systematic review of the literature on the spectrum of features detected by echocardiography and cardiac MRI. Articles were searched in Pubmed, Cochrane Library, and Biomed Central. Only papers published in English and in peer-reviewed journals up to November 2021 were selected. After an initial evaluation, 596 records were screened; the literature search identified 19 relevant articles. (3) Results: The imaging findings associated with BrS were as follows: right ventricular dilation, right ventricular wall motion abnormalities, delayed right ventricular contraction, speckle and feature tracking abnormalities, late gadolinium enhancement, and fat infiltration in the right ventricle. Furthermore, these features emerged more frequently in patients carrying the genetic mutation on the sodium voltage-gated channel α-subunit 5 (SCN5A) gene. (4) Conclusions: Specific imaging features detected by echocardiography and cardiac magnetic resonance are associated with BrS. However, this population appears to be heterogeneous and imaging anomalies emerged to be more frequent in patients carrying genetic mutations of SCN5A. Future studies with an evaluation of BrS patients are needed to identify the specific association linking the Brugada pattern, imaging abnormalities and their possible correlation with prognosis. Full article

A healthy articular cartilage is paramount to joint function. Cartilage defects, whether acute or chronic, are a significant source of morbidity. This review summarizes various imaging modalities used for cartilage assessment. While radiographs are insensitive, they are still widely used to indirectly assess cartilage. Ultrasound has shown promise in the detection of cartilage defects, but its efficacy is limited in many joints due to inadequate visualization. CT arthrography has the potential to assess internal derangements of joints along with cartilage, especially in patients with contraindications to MRI. MRI remains the favored imaging modality to assess cartilage. The conventional imaging techniques are able to assess cartilage abnormalities when cartilage is already damaged. The newer imaging techniques are thus targeted at detecting biochemical and structural changes in cartilage before an actual visible irreversible loss. These include, but are not limited to, T2 and T2* mapping, dGEMRI, T1ρ imaging, gagCEST imaging, sodium MRI and integrated PET with MRI. A brief discussion of the advances in the surgical management of cartilage defects and post-operative imaging assessment is also included. Full article

Glioblastoma multiforme (GBM) represents the most common and aggressive central nervous system tumor associated with a poor prognosis. The aim of this study was to depict the role of intraoperative imaging techniques in GBM surgery and how they can ensure the maximal extent of resection (EOR) while preserving the functional outcome. The authors conducted a systematic review following PRISMA guidelines on the PubMed/Medline and Scopus databases. A total of 1747 articles were identified for screening. Studies focusing on GBM-affected patients, and evaluations of EOR and functional outcomes with the aid of advanced image-guided techniques were included. The resulting studies were assessed for methodological quality using the Risk of Bias in Systematic Review tool. Open Science Framework registration DOI 10.17605/OSF.IO/3FDP9. Eighteen studies were eligible for this systematic review. Among the selected studies, eight analyzed Sodium Fluorescein, three analyzed 5-aminolevulinic acid, two evaluated IoMRI imaging, two evaluated IoUS, and three evaluated multiple intraoperative imaging techniques. A total of 1312 patients were assessed. Gross Total Resection was achieved in the 78.6% of the cases. Follow-up time ranged from 1 to 52 months. All studies assessed the functional outcome based on the Karnofsky Performance Status scale, while one used the Neurologic Assessment in Neuro-Oncology score. In 77.7% of the cases, the functional outcome improved or was stable over the pre-operative assessment. Combining multiple intraoperative imaging techniques could provide better results in GBM surgery than a single technique. However, despite good surgical outcomes, patients often present a neurocognitive decline leading to a marked deterioration of the quality of life. Advanced intraoperative image-guided techniques can allow a better understanding of the anatomo-functional relationships between the tumor and the surrounding brain, thus maximizing the EOR while preserving functional outcomes. Full article

Maximal safe resection is the mainstay of treatment in the neurosurgical management of gliomas, and preserving functional integrity is linked to favorable outcomes. How these modalities differ in their effectiveness on the extent of resection (EOR), survival, and complications remains unknown. A systematic literature search was performed with the following inclusion criteria: published between 2005 and 2022, involving brain glioma surgery, and including one or a combination of intraoperative modalities: intraoperative magnetic resonance imaging (iMRI), awake/general anesthesia craniotomy mapping (AC/GA), fluorescence-guided imaging, or combined modalities. Of 525 articles, 464 were excluded and 61 articles were included, involving 5221 glioma patients, 7(11.4%) articles used iMRI, 21(36.8%) used cortical mapping, 15(24.5%) used 5-aminolevulinic acid (5-ALA) or fluorescein sodium, and 18(29.5%) used combined modalities. The heterogeneity in reporting the amount of surgical resection prevented further analysis. Progression-free survival/overall survival (PFS/OS) were reported in 18/61(29.5%) articles, while complications and permanent disability were reported in 38/61(62.2%) articles. The reviewed studies demonstrate that intraoperative adjuncts such as iMRI, AC/GA mapping, fluorescence-guided imaging, and a combination of these modalities improve EOR. However, PFS/OS were underreported. Combining multiple intraoperative modalities seems to have the highest effect compared to each adjunct alone. Full article

Sodium-glucose co-transporters (SGLTs) serve to reabsorb glucose in the kidney. Recently, these transporters, mainly SGLT2, have emerged as new therapeutic targets for patients with diabetes and kidney disease; by inhibiting glucose reabsorption, they promote glycosuria, weight loss, and improve glucose tolerance. They have also been linked to cardiac protection and mitigation of liver injury. However, to date, the mechanism(s) by which SGLT2 inhibition promotes systemic improvements is not fully appreciated. Using an obese TallyHo mouse model which recapitulates the human condition of diabetes and nonalcoholic fatty liver disease (NAFLD), we sought to determine how modulation of renal glucose handling impacts liver structure and function. Apart from an attenuation of hyperglycemia, Empagliflozin was found to decrease circulating triglycerides and lipid accumulation in the liver in male TallyHo mice. This correlated with lowered hepatic cholesterol esters. Using in vivo MRI analysis, we further determined that the reduction in hepatic steatosis in male TallyHo mice was associated with an increase in nuchal white fat indicative of “healthy adipose expansion”. Notably, this whitening of the adipose came at the expense of brown adipose tissue. Collectively, these data indicate that the modulation of renal glucose handling has systemic effects and may be useful as a treatment option for NAFLD and steatohepatitis. Full article

Lymphatic vessels are highly responsive to changes in the interstitial environment. Previously, we showed renal lymphatics express the Na-K-2Cl cotransporter. Since interstitial sodium retention is a hallmark of proteinuric injury, we examined whether renal sodium affects NKCC1 expression and the dynamic pumping function of renal lymphatic vessels. Puromycin aminonucleoside (PAN)-injected rats served as a model of proteinuric kidney injury. Sodium ²³Na/¹H-MRI was used to measure renal sodium and water content in live animals. Renal lymph, which reflects the interstitial composition, was collected, and the sodium analyzed. The contractile dynamics of isolated renal lymphatic vessels were studied in a perfusion chamber. Cultured lymphatic endothelial cells (LECs) were used to assess direct sodium effects on NKCC1. MRI showed elevation in renal sodium and water in PAN. In addition, renal lymph contained higher sodium, although the plasma sodium showed no difference between PAN and controls. High sodium decreased contractility of renal collecting lymphatic vessels. In LECs, high sodium reduced phosphorylated NKCC1 and SPAK, an upstream activating kinase of NKCC1, and eNOS, a downstream effector of lymphatic contractility. The NKCC1 inhibitor furosemide showed a weaker effect on ejection fraction in isolated renal lymphatics of PAN vs controls. High sodium within the renal interstitium following proteinuric injury is associated with impaired renal lymphatic pumping that may, in part, involve the SPAK-NKCC1-eNOS pathway, which may contribute to sodium retention and reduce lymphatic responsiveness to furosemide. We propose that this lymphatic vessel dysfunction is a novel mechanism of impaired interstitial clearance and edema in proteinuric kidney disease. Full article

Sodium (²³Na) is the most abundant cation present in the human body and is involved in a large number of vital body functions. In the last few years, the interest in Sodium Magnetic Resonance Imaging (²³Na MRI) has considerably increased for its relevance in physiological and physiopathological aspects. Indeed, sodium MRI offers the possibility to extend the anatomical imaging information by providing additional and complementary information on physiology and cellular metabolism with the heteronuclear Magnetic Resonance Spectroscopy (MRS). Constraints are the rapidly decaying of sodium signal, the sensitivity lack due to the low sodium concentration versus ¹H-MRI induce scan times not clinically acceptable and it also constitutes a challenge for sodium MRI. With the available magnetic fields for clinical MRI scanners (1.5 T, 3 T, 7 T), and the hardware capabilities such as strong gradient strengths with high slew rates and new dedicated radiofrequency (RF) sodium coils, it is possible to reach reasonable measurement times (~10–15 min) with a resolution of a few millimeters, where it has already been applied in vivo in many human organs such as the brain, cartilage, kidneys, heart, as well as in muscle and the breast. In this work, we review the different geometries and setup of sodium coils described in the available literature for different in vivo applications in human organs with clinical MR scanners, by providing details of the design, modeling and construction of the coils. Full article